Even though the incidence of cancer increases sharply with age, the disease becomes less common in people who reach older ages (80 years and over). This mysterious phenomenon is believed to be due to a loss of regenerative potential of stem cells during aging.
Cancer occurs at all ages, but its incidence increases sharply during the sixth and seventh decades of life.
This increase is mainly due to the accumulation of mutations which occur spontaneously or following exposure to different risk factors (tobacco, alcohol, UV rays, obesity, certain viruses).
On the other hand, there seems to be a mysterious mechanism that manages to slow down this accumulation of mutations, because instead of continually increasing with aging, the incidence of cancer on the contrary begins to decrease in older people, who reach 80 years of age and over. .
This paradoxical effect of age on cancer risk, although known for a long time, remains an enigma.
Involvement of stem cells
It is suspected that stem cells could play an important role in this reduction in cancer risk at older ages.
First, these “mother” cells, which are the basis of the natural renewal of a tissue and its repair following an injury, are particularly vulnerable to the accumulation of mutations that can lead to cancer, because it is believed that on average, three mutations occur every time a normal human stem cell divides. As a result, a high proportion of cancers originate from these mutated stem cells (1).
Second, stem cells are known to gradually lose the ability to divide during aging, which contributes to a decrease in the functional efficiency of the body’s organs. It is quite possible, on the other hand, that this wear and tear on stem cells prevents them from growing sufficiently to form a critical mass necessary for the appearance of clinically detectable tumors.
Broken stem cells
To better understand the involvement of these stem cells, a team of researchers studied a genetically modified mouse model of lung adenocarcinoma, a common type of lung cancer that accounts for approximately 7% of all cancer deaths worldwide ( 2).
They observed that in mice aged 2 years, which is equivalent to about 70 years in humans, aging inhibits the initiation and progression of lung cancer by blocking the self-renewal of stem cells in the alveoli of the lung.
They found that as mice age, they produce more of a protein called NUPR1 that is involved in iron metabolism. Aging cells then function as if they did not have enough iron and therefore lose their ability to regenerate.
Since this regenerative capacity is directly linked to increased cancer, older mice consequently develop significantly fewer tumors than their younger counterparts.
Prevention window
These results therefore imply that the sharp increase in the incidence of cancer in people aged 50 to 70 comes from the evolution of precancerous lesions which appear in relatively young individuals, when stem cells divide regularly and at the same time accumulate potentially carcinogenic mutations.
Moreover, several autopsy studies carried out in young people (30-40 years old) have systematically observed the presence of these precancerous lesions in several organs (breast, prostate, pancreas and lung, among others). When the conditions that prevail inside the body are permissive to the acquisition of carcinogenic mutations (smoking, excess weight, poor diet, sedentary lifestyle), these lesions can then evolve into a clinically detectable cancer a few years later.
This is where prevention through lifestyle plays its important role, by creating biochemical conditions unfavorable to the development of these dormant microtumors.
This discovery means that the optimal window for preventing cancer is as early as possible in age, so as to deprive stem cells of an environment that accelerates the accumulation of mutations.
By preventing or delaying the formation of precancerous lesions for as long as possible, we allow time to work in our favor: once we reach sufficiently advanced ages, the aging of stem cells acts as a brake on the development of cancer and allows us to to spend the last years of life without having to face this disease.
So there are not only downsides to old age!
(1) Tomasetti C et coll. Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science 2017; 355: 1330-1334.
(2) Zhuang X et coll. Ageing limits stemness and tumorigenesis by reprogramming iron homeostasis. Nature, published December 4, 2024.
